Abstract：
Maple Syrup Urine Disease (MSUD) is a metabolic disease characterized by the accumulation of branched-chain amino acids (BCAA) in different tissues due to a deficit in the branched-chain alpha-ketoacid dehydrogenase complex. The most common symptoms are poor feeding, psychomotor delay, and neurological damage. However, dietary therapy is not effective. Studies have demonstrated that memantine improves neurological damage in neurodegenerative diseases, such as Alzheimer\'s and Parkinson\'s diseases. Therefore, we hypothesize that memantine, an NMDA receptor antagonist can ameliorate the effects elicited by BCAA in an MSUD animal model. For this, we organized the rats into four groups: control group (1), MSUD group (2), memantine group (3), and MSUD + memantine group (4). Animals were exposed to the MSUD model by the administration of BCAA (15.8 µL/g) (groups 2 and 4) or saline solution (0.9%) (groups 1 and 3) and treated with water or memantine (5 mg/kg) (groups 3 and 4). Our results showed that BCAA administration induced memory alterations, and changes in the levels of acetylcholine in the cerebral cortex. Furthermore, induction of oxidative damage and alterations in antioxidant enzyme activities along with an increase in pro-inflammatory cytokines were verified in the cerebral cortex. Thus, memantine treatment prevented the alterations in memory, acetylcholinesterase activity, 2\',7\'-Dichlorofluorescein oxidation, thiobarbituric acid reactive substances levels, sulfhydryl content, and inflammation. These findings suggest that memantine can improve the pathomechanisms observed in the MSUD model, and may improve oxidative stress, inflammation, and behavior alterations.
摘要：
枫糖浆尿病（MSUD）是一种代谢性疾病，其特征是由于支链α-酮酸脱氢酶复合物的缺乏而导致不同组织中支链氨基酸（BCAA）的积累。最常见的症状是喂养不良，精神运动延迟，和神经损伤。然而,饮食疗法无效。研究表明，美金刚改善神经退行性疾病的神经损伤，如阿尔茨海默氏症和帕金森氏症。因此,我们假设美金刚，NMDA受体拮抗剂可以改善BCAA在MSUD动物模型中引起的作用。为此，我们将大鼠分为四组：对照组（1），MSUD组（2），美金刚组（3），和MSUD+美金刚组(4)。通过施用BCAA(15.8μL/g)(组2和4)或盐水溶液(0.9%)(组1和3)将动物暴露于MSUD模型,并用水或美金刚(5mg/kg)处理(组3和4)。我们的结果表明，BCAA管理诱导记忆改变，以及大脑皮层中乙酰胆碱水平的变化。此外，在大脑皮层中证实了氧化损伤的诱导和抗氧化酶活性的改变以及促炎细胞因子的增加。因此，美金刚治疗阻止了记忆的改变，乙酰胆碱酯酶活性，2\',7'-二氯荧光素氧化，硫代巴比妥酸活性物质水平，巯基含量,和炎症。这些发现表明，美金刚可以改善在MSUD模型中观察到的病理机制，并可能改善氧化应激，炎症,和行为改变。
